The reasons for pigment gallstone formation are currently regarded as being related to the sedimentation of bile sludge plus other factors such as deconjugation of the conjugated bilirubin by exogenous β-glucuronidase produced by bacteria in biliary tract. Moreover, many investigations demonstrated that the source of biliary bacteria is closely related to duodeno-biliary reflux due to sphincter of Oddi relaxation. The authors overview the current research status and the relevant investigations and combine them with the authors’ own related studies and reflections to discuss the relationship between duodeno-biliary reflux and pigment gallstone formation.